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Breakthrough Articles

'Breakthrough Articles’ present high-impact studies answering long-standing questions in the field of nucleic acids research and/or opening up new areas and mechanistic hypotheses for investigation. These articles are chosen by the Editors on the recommendation of Editorial Board Members and Referees. Articles are accompanied by a brief synopsis explaining the findings of the paper and where they fit in the broader context of nucleic acids research. They represent the very best papers published at NAR.

2014 Breakthrough Articles

CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism
Rammohan J, Ruiz Manzano A, Garner AL, Stallings CL, Galburt EA.
Individual bacterial species use specialized strategies and factors to regulate gene expression. The study describes the kinetic mechanism of CarD, an essential transcription factor in many bacteria including Mycobacterium tuberculosis, but not even present in others (i.e. Escherichia coli). The work also reveals a fundamental difference between the RNA polymerases from a CarD-containing and a CarD-acking bacteria and rationalizes the essentiality of CarD in species where it exists. This highlights the importance of studying non-model systems, even within the context of a highly conserved process like transcription, and advances our understanding of the physiology of this important pathogen. Free Full Text

Sequence-specific cleavage of dsRNA by Mini-III RNase
Głów D, Pianka D, Sulej AA, Kozłowski LP, Czarnecka J, Chojnowski G, Skowronek KJ, Bujnicki JM.
Deoxyribonucleases that cut double stranded DNA, such as restriction enzymes, have contributed to the revolution in biotechnology. However, thus far no anologous enzymes were available for cleavage of double stranded RNA. Here, the authors present evidence for a sequence-dependent cleavage of long dsRNA by ribonuclease Mini-III from Bacillus subtilis (BsMiniIII), a member of RNase III superfamily. These results suggest that BsMiniIII may serve as a prototype of a sequence-specific dsRNase that could possibly be developed towards a “restriction enzyme for RNA.” Free Full Text

A systematic survey of the Cys2His2 zinc finger DNA-binding landscape
Persikov AV, Wetzel JL, Rowland EF, Oakes BL, Xu DJ, Singh M, Noyes MB.
Cys2-His2 zinc fingers (C2H2-ZFs) are the most abundant class of DNA-binding proteins in higher organisms, and have been implicated in a wide range of biological processes. Furthermore, C2H2-ZFs can be engineered to specifically target genomic regions for therapeutic or other applications. Nevertheless, our understanding of how C2H2-ZFs specify their targets remains incomplete. To help bridge this gap in fundamental knowledge, the authors have performed a comprehensive series of screens to detect and quantify C2H2-ZF – DNA interactions. This work provides new insights into the complex DNA-binding landscapes of C2H2-ZFs, and serves as a valuable resource for further investigation of this important domain. Free Full Text